Chronic infection with a virus or mycoplasma is a leading possibility in the search for the cause of rheumatoid arthritis and other connective tissue disorders including Reiter's syndrome and systemic lupus erythematosus. Differences in several metabolic functions have been reported between rheumatoid and non-rheumatoid synovial cells in culture. Up to the present time exploration of these differences has not provided information regarding the etiology of connective tissue diseases. Reported differences in susceptibility of rheumatoid and non-rheumatoid synovial cells to infection with a number of viruses have not been confirmed. We recently observed that peripheral blood leukocytes from patients with rheumatoid arthritis are cytotoxic for rheumatoid synovial cells. Our immediate objective in the continued study on the role of infectious agents in rheumatoid arthritis is to determine whether the cytotoxic activity of rheumatoid leukocytes for a rheumatoid synovial cells is specific for an antigen in the rheumatoid synovial cells or whether rheumatoid leukocytes are cytotoxic for other synovial cells and cells from other tissues. We anticipate that studies will permit determining whether there is a specific antigen in synovial cell cultures or whether the rheumatoid leukocytes are "activated" and cytotoxic for cells in a non-specific way. If the reaction appears to be due to a specific antigen we anticipate studies will clarify whether the antigen is hereditary or acquired.